Comprehensive Characterization of the Coding and Non-coding Single Nucleotide Polymorphisms in the Tumor Protein p63 (TP63) Gene Using In Silico Tools.

Single Nucleotide Polymorphisms (SNPs) help to understand the phenotypic variations in humans. Numerous studies have examined the association of SNPs with various complex diseases. Researchers have identified the association of SNPs of genes through Genome-wide association study (GWAS). A number of GWAS have identified a loci located in the TP63 gene to be significantly associated with the risk of urinary bladder cancer. However, there is not any study characterizing the SNPs located at the TP63 gene for their functional and structural significance. Hence, the study aimed to comprehensively characterize SNPs in the human TP63 gene for their functional and structural significance. We investigated and evaluated the genomic variations affecting the expression, structure, and function of the TP63 protein. The study systematically retrieved nsSNPs information for the TP63 gene from the dbSNP database. We screened and analyzed both nsSNPs and non-coding SNPs in TP63 protein using a wide variety of computational tools to find the risk of pathogenicity. A total of 17 nsSNPs were identified using the 13 bioinformatics tools (i.e., SIFT, CADD, PROVEAN, PolyPhen2, PANTHER, PhD-SNP, SNP&GO, I-Mutant 2.0, ClinVar, Mutpred2, ConSurf, HOPE, and Mutation 3D) along with domain analysis. These pathogenic mutations cause a decrease in protein stability according to I-Mutant2.0. HOPE predicted 17 SNPs to have significant effect on TP63 protein structure and function. 12 nsSNPs were found in highly conserved position in TP63 inferring the damaging effect on the structure and function of the protein. Swiss PDB Viewer showed loss of hydrogen bonds and increased energy due to the SNPs. Molecular docking showed the reduction of the binding affinity of proteins for DNA and loss of hydrogen bonds. Six non-coding SNPs were found in miRNA binding sites in gene showing the effect on protein regulation using PolymiRTS and five non-coding SNPs were identified in single tissue expression quantitative trait loci (eQTL) in lung tissue, heart tissue (LV), and cerebral hemisphere (Brain) according to GTEx portal. The characterization of nsSNPs and non-coding SNPs will support researchers to focus on TP63 gene loci and ascertain their association with certain diseases.

Syntax-Semantic Types and Lexico-Semantic Models of Multi-Component Words in Old Bulgarian and Church Slavonic: Composita Substantiva & Verba

The proposed article examines the syntactic-semantic types and the lexico-semantic models of multi-component complex words from the category of substantives and verbs in Old Bulgarian and Church Slavonic. The study is done on lexical material, excerpted from the main lexicography works in Old Bulgarian and Church Slavonic languages. The analysis proceeds from the theoretical statement that the structural significance of word order (as well as of any language unit that is semantically and formally dissected) is not a simple sum of lexical meanings of its constituent units, but interactions between them on the basis of certain predicate relations. Based on the specific analysis, the conclusion is drawn that the variety of syntactic-semantic types and the lexico-semantic models of multicomponent complex words reveals the rich word-forming capabilities of the Old Bulgarian language, respectively the Church-Slavic language, and their ability to adequately translate foreign language specimens by their own means of speech.

United States

This technical note considers the regulation and supervision of fund management and equity and derivatives trading in the United States (U.S.). As one of the main destinations for household savings and a key provider of funding to U.S. corporates, investment funds play a major role in the U.S. financial system. Distortions to equity trading could cause significant loss of confidence in markets, while international post-crisis reforms for OTC derivatives have underlined the importance of greater transparency and the value of central clearing. U.S. companies have also traditionally raised more finance through equity and other capital markets than through bank lending, and so capital markets are of greater structural significance in the U.S. than in some other jurisdictions.

“Chinese Style” in architecture and planning of London (1811–1820)

Статья посвящена обоснованию структурного значения китайского стиля (шинуазри) для архитектуры Англии периода Регентства. Английская китайщина активно развивалась в садах и декоративно-прикладном искусстве, согласуясь с классическими стилями XVIII века и эклектикой XIX столетия. Происходившие синхронно перемены в архитектуре и планировке британской столицы, отвечая логике собственного развития Лондона, стали отчасти результатом контактов с Поднебесной империей и вдохновлялись примером цинского Пекина. В статье показано, что улица Риджент-стрит, связавшая исторический центр Лондона с Риджентс-парком, явилась первой расположенной по оси север-юг столичной магистралью, которая определила начало возвращения города к принципам регулярной планировки. The article shows the structural significance of the Chinese style (chinoiserie) for the architecture of England during the Regency period. The Chinese style actively developed in English gardens and decorative art, consistent with the classical styles of the 18th century and the eclecticism of the 19th century. Some changes in the architecture and planning of the British capital, which were in line with the logic of Londons own development, were also the result of contacts with the Qing Empire (16441911) and were inspired by the example of Beijing. The article shows that Regent Street, which connected the historical center of London with Regents Park, was the first Londons highway located along the north-south axis and determined the beginning of the citys return to the principles of regular planning.